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Caribbean and La Réunion Chikungunya Virus Isolates Differ in Their Capacity To Induce Proinflammatory Th1 and NK Cell Responses and Acute Joint Pathology.

Publication ,  Journal Article
Teo, T-H; Her, Z; Tan, JJL; Lum, F-M; Lee, WWL; Chan, Y-H; Ong, R-Y; Kam, Y-W; Leparc-Goffart, I; Gallian, P; Rénia, L; de Lamballerie, X; Ng, LFP
Published in: Journal of virology
August 2015

Chikungunya virus (CHIKV) is a mosquito-borne arthralgic alphavirus that has garnered international attention as an important emerging pathogen since 2005. More recently, it invaded the Caribbean islands and the Western Hemisphere. Intriguingly, the current CHIKV outbreak in the Caribbean is caused by the Asian CHIKV genotype, which differs from the La Réunion LR2006 OPY1 isolate belonging to the Indian Ocean lineage. Here, we adopted a systematic and comparative approach against LR2006 OPY1 to characterize the pathogenicity of the Caribbean CNR20235 isolate and consequential host immune responses in mice. Ex vivo infection using primary mouse tail fibroblasts revealed a weaker replication efficiency by CNR20235 isolate. In the CHIKV mouse model, CNR20235 infection induced an enervated joint pathology characterized by moderate edema and swelling, independent of mononuclear cell infiltration. Based on systemic cytokine analysis, localized immunophenotyping, and gene expression profiles in the popliteal lymph node and inflamed joints, two pathogenic phases were defined for CHIKV infection: early acute (2 to 3 days postinfection [dpi]) and late acute (6 to 8 dpi). Reduced joint pathology during early acute phase of CNR20235 infection was associated with a weaker proinflammatory Th1 response and natural killer (NK) cell activity. The pathological role of NK cells was further demonstrated as depletion of NK cells reduced joint pathology in LR2006 OPY1. Taken together, this study provides evidence that the Caribbean CNR20235 isolate has an enfeebled replication and induces a less pathogenic response in the mammalian host.The introduction of CHIKV in the Americas has heightened the risk of large-scale outbreaks due to the close proximity between the United States and the Caribbean. The immunopathogenicity of the circulating Caribbean CHIKV isolate was explored, where it was demonstrated to exhibit reduced infectivity resulting in a weakened joint pathology. Analysis of serum cytokine levels, localized immunophenotyping, and gene expression profiles in the organs revealed that a limited Th1 response and reduced NK cells activity could underlie the reduced pathology in the host. Interestingly, higher asymptomatic infections were observed in the Caribbean compared to the La Réunion outbreaks in 2005 and 2006. This is the first study that showed an association between key proinflammatory factors and pathology-mediating leukocytes with a less severe pathological outcome in Caribbean CHIKV infection. Given the limited information regarding the sequela of Caribbean CHIKV infection, our study is timely and will aid the understanding of this increasingly important disease.

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Published In

Journal of virology

DOI

EISSN

1098-5514

ISSN

0022-538X

Publication Date

August 2015

Volume

89

Issue

15

Start / End Page

7955 / 7969

Related Subject Headings

  • Virology
  • Th1 Cells
  • Reunion
  • Mice, Inbred C57BL
  • Mice
  • Killer Cells, Natural
  • Joints
  • Humans
  • Female
  • Disease Models, Animal
 

Citation

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Chicago
ICMJE
MLA
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Teo, T.-H., Her, Z., Tan, J. J. L., Lum, F.-M., Lee, W. W. L., Chan, Y.-H., … Ng, L. F. P. (2015). Caribbean and La Réunion Chikungunya Virus Isolates Differ in Their Capacity To Induce Proinflammatory Th1 and NK Cell Responses and Acute Joint Pathology. Journal of Virology, 89(15), 7955–7969. https://doi.org/10.1128/jvi.00909-15
Teo, Teck-Hui, Zhisheng Her, Jeslin J. L. Tan, Fok-Moon Lum, Wendy W. L. Lee, Yi-Hao Chan, Ruo-Yan Ong, et al. “Caribbean and La Réunion Chikungunya Virus Isolates Differ in Their Capacity To Induce Proinflammatory Th1 and NK Cell Responses and Acute Joint Pathology.Journal of Virology 89, no. 15 (August 2015): 7955–69. https://doi.org/10.1128/jvi.00909-15.
Teo T-H, Her Z, Tan JJL, Lum F-M, Lee WWL, Chan Y-H, et al. Caribbean and La Réunion Chikungunya Virus Isolates Differ in Their Capacity To Induce Proinflammatory Th1 and NK Cell Responses and Acute Joint Pathology. Journal of virology. 2015 Aug;89(15):7955–69.
Teo, Teck-Hui, et al. “Caribbean and La Réunion Chikungunya Virus Isolates Differ in Their Capacity To Induce Proinflammatory Th1 and NK Cell Responses and Acute Joint Pathology.Journal of Virology, vol. 89, no. 15, Aug. 2015, pp. 7955–69. Epmc, doi:10.1128/jvi.00909-15.
Teo T-H, Her Z, Tan JJL, Lum F-M, Lee WWL, Chan Y-H, Ong R-Y, Kam Y-W, Leparc-Goffart I, Gallian P, Rénia L, de Lamballerie X, Ng LFP. Caribbean and La Réunion Chikungunya Virus Isolates Differ in Their Capacity To Induce Proinflammatory Th1 and NK Cell Responses and Acute Joint Pathology. Journal of virology. 2015 Aug;89(15):7955–7969.

Published In

Journal of virology

DOI

EISSN

1098-5514

ISSN

0022-538X

Publication Date

August 2015

Volume

89

Issue

15

Start / End Page

7955 / 7969

Related Subject Headings

  • Virology
  • Th1 Cells
  • Reunion
  • Mice, Inbred C57BL
  • Mice
  • Killer Cells, Natural
  • Joints
  • Humans
  • Female
  • Disease Models, Animal